Sunday, July 29, 2007

Six Killers

They are the leading causes of illness and death in the United States today: heart disease, cancer, stroke, chronic obstructive pulmonary disease, diabetes and Alzheimer's disease, in that order. And they have a lot in common.

They are expensive - together, they account for 25 percent of the nation's annual health care expenditures, said Jonathan Skinner, a health economist at Dartmouth College.

They come in clusters - accumulations of plaque in arteries lead to heart attacks but also can lead to strokes and predispose to Alzheimer's disease. Diabetes can lead to heart disease, stroke and even cancer. Smoking can lead to chronic obstructive pulmonary disease as well as cancer and heart disease, which in turn predisposes to Alzheimer's.

And the outlook for them is improving - people are getting the diseases later in life, and death rates are falling.

Yet, in many instances, patients are undertreated or treated inappropriately. In some cases, science has not offered answers, but in others, the medical system has been unable to turn proven remedies into everyday care.

Friday, July 27, 2007

It is widely held that chronic pain is like a cerebral mountain gorge, carved into the landscape by torrents of pain flowing through it. This idea probably originated in the rich and colorful literature on amputation phantoms. Pain of peripheral tissue origin experienced in the limb prior to amputation is said to become “centralized”, or “burned into the brain”, where it be-comes therapeutically inaccessible. The typical story is of a persistent painful lesion or a cramp in the leg. The amputee swears that the same pain can still be felt in the phantom limb after amputation. This is called phantom “pain memory” (Katz and Melzack 1990). But be-lief in pain centralization is by no means limited to phantom limb sensation in amputees. The concept has been applied to virtually all persistent pains that have the impertinence of refusing to go away (e.g. Kalso, 1997).

A natural corollary of the idea of pain centralization is the belief that one should be able to prevent the transition of pain from acute (and treatable) to chronic (and intractable) by apply-ing analgesic modalities early and aggressively (Wall 1988). That is, if the pain of a periph-eral injury is stopped using nerve blocks or other analgesic strategies, the transition to a per-manent intractable form will be preempted. “If you wait, it will be too late !” Unaccounta-bly, this dictum has attached itself with particular strength to certain specific chronic pain con-ditions, notably phantom limb pain and chronic regional pain syndrome (CRPS, previously termed RSD, reflex sympathetic dystrophy), and much less so to other painful conditions such as headache or arthritis. Early, and not too well controlled attempts to capitalize therapeuti-cally on the idea of centralization raised hopes. Bach et al. (1988), for example, reported that dense presurgical spinal block would prevent the later appearance of phantom limb pain. Un-fortunately, larger and better designed studies failed to obtain this result (Nikolajsen et al. 1998; Nikolajsen and Jensen, 2001). In general, despite some reports of success, preemptive analgesia has not proved itself (Niv and Devor 1998; Moiniche et al. 2002).

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Like most other treatments ideas, the reality of pain centralization can only be documented in prospective, placebo controlled clinical trials, difficult as such trials might be from a practical and ethical point of view. Until such trials are carried out, we have essentially no compelling evidence that pain ever causes pain mechanisms to migrate from the periphery to the CNS. Indeed, there is a good deal of evidence that pain centralization does not occur. This comes from observations on chronic pain syndromes in which, unlike CRPS and phantom limbs, there are clear peripheral causes of pain and definitive treatments. For example, large numbers of patients suffer for years from painful osteoarthritis. But when hip replacement surgery is car-ried out, the hip pain is nearly always eliminated without leaving a centralized trace. Like-wise, the pain of childbirth does not persist for long after delivery, and the pain of a kidney stone typically ceases rapidly once the stone has passed. If pain centralization were in fact a robust and common phenomenon, every pain we ever felt would still be felt. In contrast to cen-tralization, pain of peripheral origin often does initiate a spinal amplification state that has been called "central sensitization". This is a transient phenomenon, however, and it fades away within minutes or hours after removal of the precipitating noxious event (Torebjork et al., 1992; Gracely et al., 1992). Although the terms sound the same, "centralization" and "central sensitization" are very different concepts.

Exhibition: A painful pleasure

Stefan Klein

Artistic and medical views of pain go on show in Berlin

Three bodies writhe in agony. Their limbs are distorted, their features unrecognizable, their entrails burst out. The Crucifixion triptych by Francis Bacon (the central panel of which is shown here) had no religious meaning for the painter, for whom the work was simply about the expression of extreme sensation. In Tiepolo's painting of the martyrdom of Saint Agatha, the young woman's ecstatic gaze is thrown heavenwards as she awaits the blow of her tormenter's sword. These two paintings are the artistic highlights of the exhibition Schmerz (Pain), which runs until 5 August at the Medical History Museum of Humboldt University and the neighbouring Hamburger Bahnhof Museum in Berlin.

The exhibition brings together artistic and medical views of pain. Opposite Bacon's Crucifixion is a glass cabinet containing pathological preparations of organs. Under the title 'The pleasure of pain', Tiepolo's Agatha is displayed along with forensic photographs showing fatal accidents that occurred during masochistic sex. The borders between art and documentation begin to blur, which makes the exhibits all the more disturbing. Video interviews with people who self-mutilate, by German film director Valenska Griesebach, could easily be from the files of a psychiatrist. And what differentiates a display in a vitrine from a pathology lab or an art installation?

The exhibition aims to show pain in all its forms, rather than to understand it, and plays with superficial similarities between different depictions. A video by Bruce Naumanns in which a violin string is repeatedly plucked appears next to chattering patch-clamp recordings in the only exhibit that gives a nod to neurophysiological research on pain. That's not enough to justify the exhibition's claim to build a bridge between science and art. Rather, wandering through this labyrinth of abominations, the question that comes most immediately to mind is why Christianity really needed to glorify this most ugly of all human sensations into the pinnacle of mystical experience.

Thursday, July 26, 2007

Scratch No More: Gene For Itch Sensation Discovered

Science Daily — Itching for a better anti-itch remedy? Your wish may soon be granted now that scientists at Washington University School of Medicine in St. Louis have identified the first gene for the itch sensation in the central nervous system. The discovery could rapidly lead to new treatments directly targeting itchiness and providing relief for chronic and severe itching.

The "itch gene" is GRPR (gastrin-releasing peptide receptor), which codes for a receptor found in a very small population of spinal cord nerve cells where pain and itch signals are transmitted from the skin to the brain. The researchers, led by Zhou-Feng Chen, Ph.D., found that laboratory mice that lacked this gene scratched much less than their normal cage-mates when given itchy stimuli.

The laboratory experiments confirmed the connection between GRPR and itching, offering the first evidence of a receptor specific for the itch sensation in the central nervous system. The findings are reported in Nature.

This is the first new book in many years to provide a comprehensive review of the latest theory, research, and treatment of chronic headaches from a biopsychological perspective. It is designed to make the tools of assessment and therapy widely accessible, while placing them in the context of how the disorders arise. The physiology and psychology of pain, and each disorder, are reviewed in an accessible manner. Clinical experience, laboratory data, and illustrative vignettes aid in treatment selection.

Part I introduces the major types of headaches and provides a comprehensive review of pain. Part II details the major forms of headaches—migraine, tension-type, cluster, secondary, and headaches in children. A clinical presentation introduces each type of headache, followed by the physiological and psychological underpinnings and their implications for assessing and treating patients. Part III serves as a clinical guide for practitioners. The book closes with an analysis of how well the treatments work, the mechanisms behind the efficacy, and guidelines for treatment matching.

A range of practical tools is incorporated. Clinical evaluation is reviewed in depth, including the interview, psychometrics, and psychophysiological assessment. Key sections of the 2004 International Headache Society diagnostic criteria serve as a “mini” diagnostic manual. Tables allow rapid look-up of the various disorders and their distinguishing characteristics; trigger point referral patterns; and the comparative merits of migraine medications. Blank headache diaries, appropriate for various stages of treatment, serve as models. A relaxation exercise is provided, as are muscle tension and hand temperature norms. Key terms are defined in the extensive glossary to help psychologists and medical professionals share vocabulary. Medical, herbal, and behavioral therapies are discussed in terms of the underlying science.

Wednesday, July 11, 2007

Endo Pharmaceuticals Holdings Inc. said Wednesday its skin patch candidate aimed at delivering pain and inflammation treatment ketoprofen failed two late-stage clinical trials, forcing the company to withdraw guidance on when it might apply for Food and Drug Administration approval.

The drug developer had previously expected to file for approval in during the first half of 2008. The patch, being developed for the treatment of soft-tissue injuries, failed Phase III clinical trials dealing with ankle sprains and strains and pain associated with tendonitis or bursitis of the shoulder, elbow or knee. It failed to work any better than placebo in the studies.

A third Phase III clinical trial, also studying the patch as a treatment for tendonitis or bursitis of the shoulder, elbow or knee, is ongoing.

"Our initial view is that the results of the first two Phase III trials illustrate the difficulty of demonstrating a statistically significant separation between the treated and control groups in clinical studies involving topical patches," said Chief Scientific Officer Dr. David A. Lee. "Before determining our next course of action, we intend to review the results of these two trials in relation to the positive placebo-controlled trials conducted in Europe."

Tuesday, July 10, 2007

A New Focus on Easing the Pain Palliative Care Helps The Very Ill. It May Also Keep Costs Down.

David Thibault grows orchids as a hobby, but the elegant flower on his bedside tray did little to lift his spirits. He stared out the window of his room at George Washington University Hospital, waiting for lab results that could tell him if he had months, weeks or maybe only days to live.

A month earlier, in April, Thibault and his wife, Judy Thibault Klevins, had been preparing for a trip to Japan when he felt pain that was different from the pain he had long experienced from Crohn's disease, an inflammatory bowel ailment. It turned out to be small-bowel cancer. If the disease weren't so rare, he now ventured aloud, maybe more research money would have gone into it, maybe he wouldn't be facing death at age 67.

Joan Panke, a nurse practitioner, listened intently. The coordinator of GW's Palliative Care Service, Panke and her team ease the pain of those with serious or terminal illness. They walk families like the Thibaults through the difficult work of understanding options, making decisions and, sometimes, trying to find a measure of peace as they say goodbye.

Monday, July 09, 2007

Over the course of three days recently, I had 23 head-to-toe physicals from 23 second-year students at the Georgetown School of Medicine. I was the first person these would-be doctors had ever fully examined on their own. Some were shaking so violently when they approached me with their otoscopes—the pointed device for looking in the ear—that I feared an imminent lobotomy. Some were certain about the location of my organs, but were stymied by the mechanics of my hospital gown and drape. And a few were so polished and confident that they could be dropped midseason into Grey's Anatomy.